Subcellular localization of the alphaherpesvirus serine/threonine kinase Us3 as a determinant of Us3 function

Finnen, Renée L.; Banfield, Bruce W.

doi:10.4161/viru.1.4.11980

Cited by 8 publications

(7 citation statements)

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“…We recently reported that treatment of herpes simplex virus type 2 (HSV-2) Us3 -transfected and HSV-2-infected cells with leptomycin B (LMB), a specific inhibitor of nuclear export mediated by chromosomal regional maintenance protein (CRM1), resulted in nuclear trapping of Us3 (Finnen et al, 2010). Furthermore, we found that Us3-induced filamentous process formation was diminished when Us3 was trapped within the nucleus, providing evidence that Us3 subcellular localization can impact its biological function (Finnen and Banfield, 2010; Finnen et al, 2010). Thus, the ability to shuttle between the nucleus and the cytoplasm may be vital for HSV-2 Us3 functionality.…”

Section: Introductionmentioning

confidence: 58%

Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3

et al. 2011

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The alphaherpesvirus serine/threonine kinase Us3 plays diverse roles in virus multiplication and modifies both nuclear and cytoplasmic substrates. We recently reported that treatment of HSV-2 Us3-transfected and HSV-2-infected cells with leptomycin B, an inhibitor of nuclear export mediated by interaction of chromosomal regional maintenance protein (CRM1) with leucine rich nuclear export signals (NESs), resulted in nuclear trapping of Us3. Here, we utilized fluorescence loss in photobleaching to monitor nuclear export of HSV-2 Us3 and confirm that this process proceeds solely via a CRM1-mediated mechanism. Analysis of deletion derivatives of HSV-2 Us3 fused to a nuclear export reporter protein implicated the involvement of NES-like sequences in nuclear export. However, nuclear trapping of HSV-2 Us3 proteins carrying mutations in these potential NESs was not observed, indicating these sequences are not functional in the context of full-length protein. Our analyses also revealed previously unidentified regions of HSV-2 Us3 that contribute to its kinase activity.

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Section: Introductionmentioning

confidence: 58%

Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3

et al. 2011

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“…[126][127][128][129] However, an exception to this is the chicken alphaherpesvirus MDV. Intact and kinase-inactive US3 of MDV display equal abilities to induce actin rearrangements, although these are less dramatic compared with those of other alphaherpesviruses, as MDV US3 induces actin stress fiber disassembly but has not been reported to induce cell projections.…”

Section: E28318-8mentioning

confidence: 99%

Rho’ing in and out of cells

2014

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These authors contributed equally to this work Keywords: Rho GTPase, actin, egress, entry, gene expression, immune system, transformation, virus Rho GTPases are key regulators of actin and microtubule dynamics and organization. increasing evidence shows that many viruses have evolved diverse interactions with Rho GTPase signaling and manipulate them for their own benefit. in this review, we discuss how Rho GTPase signaling interferes with many steps in the viral replication cycle, especially entry, replication, and spread. Seen the diversity between viruses, it is not surprising that there is considerable variability in viral interactions with Rho GTPase signaling. However, several largely common effects on Rho GTPases and actin architecture and microtubule dynamics have been reported. For some of these processes, the molecular signaling and biological consequences are well documented while for others we just begin to understand them. A better knowledge and identification of common threads in the different viral interactions with Rho GTPase signaling and their ultimate consequences for virus and host may pave the way toward the development of new antiviral drugs that may target different viruses.©2014 Landes Bioscience. Do not distribute. e28318-2Small GTPases volume 5effector of ROCK, which phosphorylates and inhibits cofilin.14 Cofilin is an F-actin-severing protein. Mainly depending on the local availability of G-actin monomers, cofilin activity may lead to net actin depolymerization or increased actin polymerization and branching. Other RhoA effectors include members of the ezrin/radixin/moesin (ERM) proteins 15 . Rac1 is thought to release WAVE from an inhibited complex, thereby activating the actin-polymerizing complex Arp2/3. 16,17 Active Arp2/3 mediates branching and elongation of existing actin filaments, generating a meshwork. Cdc42 also activates Arp2/3 through a direct interaction with the Arp2/3 activators Wiskott-Aldrich syndrome protein (WASP) or N-WASP.18 Both Rac1 and Cdc42 also activate group I serine/threonine p21 activating kinases (PAK). These different signalization branches are interconnected. In general, RhoA pathway signaling counteracts the Rac1 and Cdc42 signaling axes and vice versa.Because Rho GTPase signaling is involved in a plethora of cellular processes, it is perhaps not surprising that several viral gene products have evolved to interfere with and modulate these signaling axes. Indeed, several viruses interfere with the actin cytoskeleton and Rho GTPase signaling during many steps of their replication cycle. During entry and egress, these interactions may allow or facilitate viral particle passage across the cortical actin barrier and to rearrange actin to conformations that promote virus infection and spread, while other viral processes, such as intracellular movement, gene expression and latency, but also interaction with the immune system or oncogenesis may also depend to some extent on Rho GTPase signaling and associated actin rearrangements. In this review, the current kno...

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“…PrV infection leads to actin stress fibre breakdown and formation of actin protrusions, all dependent on pUS3 activity and associated with increased cell-to-cell spread [ 81 ]. Comparable pUS3-induced actin network changes have been seen in HSV-2 and other alphaherpesviruses, including Marek’s disease virus (MDV), which infects chickens [ 84 , 88 , 89 ], bovine herpesvirus type 5 (BHV-5) [ 90 ] and equine herpesvirus type 1 (EHV-1) where pUS3 is also important for efficient nuclear egress [ 91 ].…”

Section: Filamentous Actinmentioning

confidence: 99%

Cytoskeletons in the Closet—Subversion in Alphaherpesvirus Infections

Denes

Miranda-Saksena

Cunningham

et al. 2018

Viruses

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Actin filaments, microtubules and intermediate filaments form the cytoskeleton of vertebrate cells. Involved in maintaining cell integrity and structure, facilitating cargo and vesicle transport, remodelling surface structures and motility, the cytoskeleton is necessary for the successful life of a cell. Because of the broad range of functions these filaments are involved in, they are common targets for viral pathogens, including the alphaherpesviruses. Human-tropic alphaherpesviruses are prevalent pathogens carried by more than half of the world’s population; comprising herpes simplex virus (types 1 and 2) and varicella-zoster virus, these viruses are characterised by their ability to establish latency in sensory neurons. This review will discuss the known mechanisms involved in subversion of and transport via the cytoskeleton during alphaherpesvirus infections, focusing on protein-protein interactions and pathways that have recently been identified. Studies on related alphaherpesviruses whose primary host is not human, along with comparisons to more distantly related beta and gammaherpesviruses, are also presented in this review. The need to decipher as-yet-unknown mechanisms exploited by viruses to hijack cytoskeletal components—to reveal the hidden cytoskeletons in the closet—will also be addressed.

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Subcellular localization of the alphaherpesvirus serine/threonine kinase Us3 as a determinant of Us3 function

Cited by 8 publications

References 40 publications

Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3

Nucleocytoplasmic shuttling of the HSV-2 serine/threonine kinase Us3

Rho’ing in and out of cells

Cytoskeletons in the Closet—Subversion in Alphaherpesvirus Infections

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